Pharmacological studies of 1-(2,3-dimethyl-4-methoxyphenyl)-2-methyl-3-(1-pyrrolidinyl)-1- propanone hydrochloride (AD-2239), a centrally acting muscle relaxant

Arch Int Pharmacodyn Ther. 1985 May;275(1):105-22.

Abstract

Centrally acting muscle relaxant properties of AD-2239 were compared with those of tolperisone, eperisone, diazepam and baclofen. AD-2239 dose-relatedly depressed extensor reflex in urethane-chloralose anesthetized intact and spinal rats, the i.v. potencies being similar to those of tolperisone and eperisone. These effects of AD-2239 were long-lasting. When orally administered, AD-2239 was 4 times more potent than eperisone. Diazepam was without effect on the extensor reflex in spinal rats. AD-2239 depressed the flexor reflex without affecting the patellar reflex in anesthetized cats. Baclofen depressed the latter. When orally administered, AD-2239, in a dose-related manner, depressed the flexor reflex in anesthetized cats, with a potency approximately 8 times that of tolperisone or eperisone. AD-2239 produced a dose-related reduction of anemic decerebrate rigidity (alpha-rigidity) in rats. The potency, at the minimum effective i.v. dose, was 4 times greater than that of tolperisone or eperisone, equal to that of diazepam, and one-half of that of baclofen. AD-2239 neither affected spontaneous electroencephalogram (EEG) nor EEG arousal response in immobilized cats, while the other drugs, at comparatively low doses, depressed them. The results strongly suggest that AD-2239 may have advantages over the existing centrally acting muscle relaxants in the treatment of human clinical spasticity and muscle spasm syndromes.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Arousal / drug effects
  • Baclofen / pharmacology
  • Behavior, Animal / drug effects
  • Cats
  • Decerebrate State
  • Diazepam / pharmacology
  • Electroencephalography
  • Electromyography
  • Female
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred Strains
  • Muscle Relaxants, Central / pharmacology*
  • Muscle Rigidity / prevention & control
  • Propiophenones / pharmacology
  • Pyrrolidines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Reflex / drug effects
  • Reflex, Stretch / drug effects
  • Species Specificity
  • Tolperisone / pharmacology

Substances

  • Muscle Relaxants, Central
  • Propiophenones
  • Pyrrolidines
  • eperisone
  • AD 2239
  • Tolperisone
  • Baclofen
  • Diazepam